San Francisco, CA (UroToday.com) Dr. Nieves Martinez Chanza from Belgium provided an overview of the AURA trial, assessing avelumab as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC). Avelumab is a fully human anti-PD-L1 IgG1 monoclonal antibody, approved in monotherapy for the advanced disease [1]. For patients with non-metastatic MIBC the current preferred treatment consists of a multimodal approach comprising neoadjuvant cisplatin-based chemotherapy followed by surgery. However, the benefit of the neoadjuvant chemotherapy is modest and an important proportion of patients do not benefit providing unnecessary toxicity and potential morbidity. Additionally, 40% of this population is ineligible for platinum-based therapies and currently no medical alternative option exists. The objective of this study was to assess several important questions:

What is the role of the immunotherapy in the neoadjuvant setting?

Is efficacy of immunotherapy influenced by the association with cytotoxic agents? - Which agents (anthracyclins, platin or taxanes)?

Do cisplatin-ineligible patients benefit from an immunotherapy approach?

Is there any predictive biomarker for chemotherapy and/or immunotherapy?

This trial is a randomized phase 2 study in patients for neoadjuvant chemotherpay followed by radical cystectomy (EudraCT Number: 2017-002758-35). The study will recruit cisplatin eligible and ineligible patients. For the group of cisplatin-eligible patients, chemotherapy with high dose of metotrexate-vinblastin-adriamycin-cisplatin or cisplatin-gemcitabine will be given with avelumab. For this group, the null hypothesis is that pathologic complete response is <25%, which should be rejected with a one-sided test at a level of 5% in case the true rate is at least 50% with a power of 90%. As such, 28 patients will be recruited to each arm. For the group of cisplatin-ineligible patients, avelumab as monotherapy or associated with paclitaxel-gemcitabine will be used. For this group, the pathologic complete response rate is ~12%, and will be required to recruit 40 patients to each arm. Four cycles of treatment will be given and a radiological evaluation will be performed after two cycles. If there is evidence of progressive disease, the neoadjuvant treatment will be stopped and the radical cystectomy performed. The primary objective is to determine the pathologic complete response rate as well as to assess the toxicity profile. Blood, urine and stool samples will be collected at different points to perform translational research.

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.